Cisplatin is a widely used chemotherapeutic agent that is clinically approved to fight both carcinomas and sarcomas. It has relatively high efficiency in treating ovarian cancers and metastatic testicular cancers. It is generally accepted that the major mechanism of cisplatin anti-cancer action is DNA damage. However, cisplatin is also effective in metastatic cancers and should, therefore, affect slow-cycling cancer stem cells in some way. In this review, we focused on the alternative effects of cisplatin that can support a good therapeutic response. First, attention was paid to the effects of cisplatin at the cellular level such as changes in intracellular pH and cellular mechanical properties. Alternative cellular targets of cisplatin, and the effects of cisplatin on cancer cell metabolism and ER stress were also discussed. Furthermore, the impacts of cisplatin on the tumor microenvironment and in the whole organism context were reviewed. In this review, we try to reveal possible causes of the unexpected effectiveness of this anti-cancer drug.

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic and Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic and BIOCEV 1st Faculty of Medicine Charles University Průmyslová 595 CZ 252 50 Vestec Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic and Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic and Central European Institute of Technology Brno University of Technology Purkynova 656 123 CZ 612 00 Brno Czech Republic

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